POS1015 SAFETY OF GUSELKUMAB IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS WHO ARE BIO-NAÏVE OR TNFi-EXPERIENCED: POOLED RESULTS FROM 4 RANDOMIZED CLINICAL TRIALS THROUGH 2 YEARS
Authors: P. Rahman, W. H. Boehncke, P. J. Mease, A. B. Gottlieb, I. Mcinnes, M. Neuhold, M. Shawi, Y. Wang, S. Sheng, P. Bergmans, A. Kollmeier, E. Theander, J. Yu, E. Leibowitz, M. Marrache, L. Coates
Journal: Annals of the Rheumatic Diseases (2022)

Background Guselkumab (GUS), a selective IL-23p19 subunit inhibitor, demonstrated efficacy and a favorable safety profile in active psoriatic arthritis (PsA) in the Phase (Ph)2 1 , Ph3 (DISCOVER [D]-1&amp;2) 2,3 , and Ph3b COSMOS 4 randomized controlled trials (RCTs). Objectives Assess GUS safety through 2 years (Y) in biologic (bio)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced (exp) active PsA patients (pts) pooled across 4 RCTs (Week [W] 56: Ph2 and COSMOS; W60: D1; W112: D2). Methods Eligible pts in COSMOS had inadequate response to 1 or 2 prior TNFi; 9% of Ph2 pts and 30% of D1 pts had 1 or 2 prior TNFi; D2 pts were bio-naïve. Incidence rates of adverse events (AEs) are summarized among all treated pts for the placebo (PBO)-controlled (W0-24) and active treatment periods through 2Y (max duration of exposure 100 W) according to actual treatment received, calculated as the number of events per 100 pt-Y of follow-up (PY), along with 95% confidence intervals (CI). Gastrointestinal (GI)-related serious AEs (SAEs) were identified using the Medical Dictionary for Regulatory Activities (MedDRA) system-organ class; major adverse cardiovascular events (MACE; predefined as MI, Stroke, or CV death) and opportunistic infections (OIs) were identified through medical review. Results Across the 4 RCTs, 1508 pts with active PsA received GUS 100 mg every 4 weeks (Q4W) or Q8W and were followed for a median of 1.2 Y, representing 2125 PY. In the overall population (N=1554), which includes PBO-treated pts that discontinued study agent prior to W24, 1138 pts were bio-naïve and 416 pts were TNFi-exp. Among all treated pts, the overall GUS safety profile was generally consistent with that of PBO through W24; rates remained low through 2Y of GUS (Table 1). The GUS safety profile was similar to that observed with PBO within the bio-naïve and TNFi-exp cohorts through W24. Incidence rates of AEs were generally consistent between cohorts in GUS-treated pts; whereas, TNFi-exp PBO-treated pts had more SAEs, study agent d/c due to AEs, and serious infections than bio-naïve PBO pts (Figure). Table 1. Overall Treatment-emergent AEs PBO-controlled (W0-24 ) a Through up to 2Y PBO b (N=517 ) GUS Q8W (N=664 ) GUS Q4W (N=373 ) Combined GUS (N=1037 ) GUS Q8W (N=664 ) GUS Q4W (N=373 ) Combined GUS c (N=1508 ) Total (median) PY 230 (0.5) 305 (0.5) 172 (0.5) 478 (0.5) 941 (1.1) 645 (2.1) 2125 (1.2) Events/100 PY (95% CI ) AEs 223 (204, 243) 233 (216, 250) 223 (201, 246) 229 (216, 243) 164 (156, 172) 139 (130, 148) 146 (141, 151) SAEs 8.7 (5.3, 13) 4.9 (2.8, 8.1) 5.2 (2.4, 9.9) 5.0 (3.2, 7.5) 6.4 (4.9, 8.2) 4.7 (3.1, 6.6) 5.7 (4.7, 6.8) AEs leading to study agent d/c 4.4 (2.1, 8.0) 3.6 (1.8, 6.5) 7.0 (3.6, 12.2) 4.8 (3.1, 7.2) 2.6 (1.6, 3.8) 2.9 (1.8, 4.6) 2.7 (2.1, 3.5) Infections 59 (50, 70) 56 (48, 65) 57 (47, 70) 57 (50, 64) 43 (38, 47) 37 (33, 42) 39 (36, 42) Serious Infections 2.2 (0.71, 5.1) 0.33 (0.01, 1.8) 1.7 (0.36, 5.1) 0.84 (0.23, 2.1) 1.7 (0.97, 2.8) 0.77 (0.25, 1.8) 1.5 (1.0, 2.1) Malignancy 0.44 (0.01, 2.4) 0.98 (0.20, 2.9) 0.00 (0.00, 1.7) 0.63 (0.13, 1.8) 0.42 (0.12, 1.1) 0.00 (0.00, 0.46) 0.28 (0.10, 0.61) MACE 0.44 (0.01, 2.4) 0.33 (0.01, 1.8) 0.58 (0.01, 3.2) 0.42 (0.05, 1.5) 0.21 (0.03, 0.77) 0.46 (0.10, 1.4) 0.24 (0.08, 0.55) GI-related SAEs 1.3 (0.27, 3.8) 0.33 (0.01, 1.8) 0.00 (0.00, 1.7) 0.21 (0.01, 1.2) 0.32 (0.07, 0.93) 0.46 (0.10, 1.4) 0.28 (0.10, 0.61) OIs 0.00 (0.00, 1.3) 0.00 (0.00, 0.98) 0.00 (0.00, 1.7) 0.00 (0.00, 0.63) 0.21 (0.03, 0.77) 0.00 (0.00, 0.46) 0.14 (0.03, 0.41) MedDRA Version 23.1. a Includes safety follow-up data through 2Y for pts who d/c study agent prior to W24 and did not receive any study agent at or after W24. b Includes data prior to GUS in PBO pts who switched from PBO to GUS. c Includes PBO to GUS cross-over at W24. Conclusion The favorable GUS safety profile demonstrated through W24 persisted through 2Y across bio-naïve and TNFi-exp pts. References [1]Deodhar A, et al. Lancet . 2018;391:2213-2224. [2]Deodhar A, et al. Lancet . 2020;395:1115-1125. [3]Mease PJ, et al. Lancet . 2020;395:1126-1136. [4]Coates LC, et al. ARD . 2021;80:140-141. OP0230. Disclosure of Interests Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Janssen, Leo, Lilly, Novartis, and UCB, Consultant of: AbbVie, Almirall, Janssen, Leo, Lilly, Novartis, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Alice B Gottlieb Consultant of: AnaptsysBio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb, Incyte, GSK, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., UCB, and Dermavant, Grant/research support from: Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB, Xbiotech, and Sun Pharma, Iain McInnes Shareholder of: Causeway Therapeutics and Evelo Compugen, Consultant of: Astra Zeneca, AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Cabaletta, Compugen, GSK, Gilead, Janssen, Novartis, Pfizer, Sanofi, Roche, and UCB, Grant/research support from: Astra Zeneca, Bristol-Myers Squibb, Amgen, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB, Marlies Neuhold Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Yanli Wang Consultant of: Janssen, Employee of: IQVIA, Shihong Sheng Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Paul Bergmans Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Biostatistics, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Elke Theander Employee of: Janssen Scientific Affairs, LLC, Jenny Yu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Evan Leibowitz Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Scientific Affairs, LLC, Marilise Marrache Shareholder of: Johnson &amp; Johnson, Employee of: Medical Affairs, Janssen Inc., Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB